We propose a series of studies designed to reveal relations between free immunoglobulin light chains and vascular diseases, particularly microvascular basement membrane thickening, occurring in patients with diabetes mellitus. This is the first phase of our general study of immunoglobulins and vascular disease. We hypothesize that microvascular disease in patients with maturity-onset diabetes mellitus is initiated by deposition of serum immunoglobulin light chains in basement membranes. In this view light chain deposits in pancreatic vessels and islets lead to insulin deficiency and the metabolic abnormalities of diabetes. This hypothesis is made because pancreatic vascular abnormalities and islet hyalinization may be attributable to light chain deposition, and because the generalized microvascular changes in diabetics appear compatible with such deposition. The hypothesis is supported by our finding of light chain overproduction in maturity-onset diabetics. We propose: (1) determination by radioimmunoassay of serum light chain levels in a larger group of diabetics in order to reveal correlations between clinical events and light chain levels; (2) determination of serum light chain levels in subjects presenting to the health Testing Center in order to reveal normal variations with age and correlations with detected clinical and laboratory abnormalities; (3) determination of serum light chain levels in acromegalics before and after trans- sphenoidal hypophysectomy and in normal subjects given growth hormone in order to reveal relations between growth hormone and light chain production; and (4) examination of skin and muscle vessels of diabetics and patients with uremia (who have elevated serum light chain levels) by light, electron and fluorescence microscopy in order to reveal possible light chain deposits.